JP6842794B2 - Topical skin preparation - Google Patents

Description

The present invention relates to an external preparation for skin.

In recent years, an increasing number of people in Japan suffer from itchy skin diseases (particularly atopic dermatitis, dry dermatitis, sensitive skin, etc.) due to changes in the living environment, rapid aging, and various stresses. These skin diseases are accompanied by strong itching and rough skin. For the treatment, external preparations containing antipruritic ingredients such as crotamiton and antihistamine and moisturizing ingredients such as heparinoids as active ingredients are used.
Of these, heparinoids are polysulfated esters of mucopolysaccharides that have a blood circulation promoting effect, and because their structures contain many sulfate groups, carboxyl groups, hydroxyl groups, etc., they have high moisturizing ability and are already dry. It is also used as an over-the-counter drug for the purpose of treating sexual skin diseases.
Dry skin (xeroderma in the elderly and adults, dry skin in children) is a typical symptom of dry skin diseases, and in the elderly and adults, due to skin aging (physiological changes with aging). It occurs because the stratum corneum is thinner in children than in adults, the amount of sebum secreted is unstable, and the barrier function is not yet stable. In either case, the skin becomes dry and rough, often accompanied by itching as a subjective symptom. The degree of itching is often strong, and the patient constantly scratches the affected area violently, resulting in increased itching, and further scratching may cause inflammation of the skin, exacerbating the symptoms, and secondary eczema.

Much research and development has been carried out for the purpose of breaking such a vicious cycle, alleviating itching, which is an unpleasant symptom, and preventing eczema (see Patent Documents 1 and 2).
Patent Document 1 discloses an external preparation containing diphenhydramine, which is an external antihistamine, and a heparinoid, and having the efficacy and effect of dry skin disease accompanied by itching. However, the action of heparinoids is to supplement the lack of water, and the action of diphenhydramine is to relieve itching, both of which are symptomatic treatments, so that skin diseases should be treated radically. Was difficult.
That is, when dry skin diseases are described by site or disease, rough fingers, keratosis of elbows / knees / heels / ankles, cracks / cracks of limbs, xerosis, dry skin of children, etc. are exemplified. To. Of these, in rough hands, xerosis, and keratosis, the action of promoting so-called turnover, in which the skin tissue presenting the condition is replaced to a normal state, is effective in treating cracked skin tissue in cracks and cracks. It was considered that each of the promoting actions was necessary. Therefore, a device was devised to add a vitamin (tocopherol acetate) that helps restore the skin tissue to a normal state and allantoin that has a skin tissue repairing action (Patent Document 2).

Japanese Unexamined Patent Publication No. 2010-180206 Japanese Unexamined Patent Publication No. 2011-231128

In spite of the above-mentioned measures, it is difficult to say that an external preparation for skin that can promote a radical treatment for a dry skin disease accompanied by itching is sufficiently provided.
The present invention has been made in view of the above circumstances, and an object of the present invention is to radically treat a dry skin disease accompanied by itching by suppressing itching and restoring the skin tissue to a normal state. To provide an external preparation for skin.

The external preparations for skin according to the invention for achieving the above objectives include (A) heparin-like substances, (B) tocopherol, tocopherol acetate, tocopherol nicotinate, tocopherol linolenate, tocopherol succinate, panthenol and vitamin A. At least one selected from the group consisting of (C) glycyrrhetinic acid, glycyrrhetinic acid, stearyl glycyrrhetinate, allantin, and at least one anti-inflammatory agent selected from the group consisting of salts thereof, and (D) diphenhydramine and It is characterized by containing at least one antipruritic agent selected from the group consisting of diphenhydramine hydrochloride.
In the present invention, the content of (A) heparin-like substance is 0.2 to 0.4% by mass (preferably 0.3% by mass), and (B) tocopherol, tocopherol acetate, tocopherol nicotinate, linolenic acid. The content of at least one selected from the group consisting of tocopherol, tocopherol succinate, pantenol and vitamin A is 0.001 to 1% by mass (preferably 0.01 to 0.8% by mass, more preferably 0.01 to 0.8% by mass). 0.1 to 0.7% by mass, more preferably 0.4 to 0.6% by mass), (C) The content of the anti-inflammatory agent is 0.01 to 5% by mass (preferably 0.05 to 0.05%). 1% by mass, more preferably 0.1 to 0.5% by mass), and (D) the content of the antipruritic agent is 0.1 to 2% by mass (preferably 0.5 to 1.5% by mass). is there.

Heparin is a type of glycosaminoglycan produced mainly in the liver in the living body. It has an anticoagulant effect, and is used as a therapeutic agent for thromboembolism / disseminated intravascular coagulation (DIC), artificial dialysis, and prevention of blood coagulation in extracorporeal circulation. The heparinoid means heparin and a substance obtained by modifying or partially decomposing heparin and having the same physiological activity as heparin.
Vitamin A means a general term for retinol, retinal, retinoic acid, their 3-dehydroforms, and derivatives thereof.
Dosage forms of external preparations for skin include, for example, creams, emulsions, ointments, gels and the like.

According to the present invention, it is possible to provide an external preparation for skin capable of radically treating a dry skin disease accompanied by itching by suppressing itching and restoring the skin tissue to a normal state.

Next, embodiments of the present invention will be described with reference to figures and tables, but the technical scope of the present invention is not limited to these embodiments, and various embodiments without changing the gist of the invention. Can be carried out at.
<Test method>
1. 1. Preparation of each composition A cream as an external preparation for skin (test composition) containing a heparinoid, tocopherol acetate, allantoin and diphenhydramine as an active ingredient was prepared.
On the other hand, as an active ingredient, a skin external preparation containing a heparinoid and diphenhydramine (comparative composition 1), and a skin external preparation containing a heparinoid, panthenol, tocopherol acetate, allantin and diphenhydramine (comparative composition 2). Prepared. In addition, in each composition, other compounding components were prepared in the same manner.
The dose of each composition was as shown in Table 1.

2. Measurement of keratin water content We evaluated the effect of improving rough skin in 5 subjects (15 in total) who complained of itching due to rough skin.
Specifically, each test composition was applied to the back of the hand in an appropriate amount before going to bed and when dryness was a concern. The electrical conductivity (μs) before use and 5 days after the start of use (after use) was measured with a surface stratum corneum water content measuring device (SKICON-200EX, manufactured by IBS Co., Ltd.). Each moisture value was shown as the average value of the measured values at three points for each subject. As the relative moisture value, the post-use moisture value / pre-use moisture value was calculated.

3. 3. Sensory evaluation test Each test composition was applied to the affected areas of 5 subjects who complained of itching due to rough skin, and evaluation was performed using the following 5 types of parameters. That is, (1) usability (5 points when it is easy to apply, 1 point when it is difficult to apply), (2) improvement of skin condition (5 points when dry skin is improved, dry skin). 1 point if the condition did not improve), (3) Anti-itch effect (5 points if the itch stopped, 1 point if the itch did not stop), (4) Suppressing the recurrence of itching (painting) 5 points for recurrence on the day when the affected area was not scratched, 1 point for recurrence on the day of application and scratching the affected area), and (5) Persistence of skin improvement (skin dried before application) 5 points were given when the condition was felt to be improved, and 1 point was given when the dry skin was not improved before application). Each parameter was evaluated on a 5-point scale.
The scores of each subject were totaled, and the total score was 21 to 25 points: ⊚, 16 to 20 points: ○, 11 to 15 points: Δ, and less than 11 points: ×.

<Test results>
Tables 2 to 4 show the water content of the keratin (before and after use) and the results of the sensory evaluation.

As shown in the above results, the test composition was superior in the relative water content (moisture value after use / moisture value before use) as compared with the comparative composition. Also, in the sensory evaluation, the value was higher than that of the comparative composition. Thus, it was clarified that the test composition is excellent in the effect of normalizing the keratin and improving the rough hands and the effect of suppressing the recurrence of itching and increasing the sustainability of the skin improvement.
<Preparation of other compositions>
Next, other compositions were prepared.
1. 1. Preparation of milky lotion A milky lotion was prepared by adding 1.0 g of cetanol, 0.5 g of stearyl alcohol, 4 g of white petrolatum, and an appropriate amount of purified water to 0.3 g of a heparinoid, 0.5 g of tocopherol acetate, 0.2 g of allantin and 1.0 g of diphenhydramine.
2. Preparation of ointment An ointment was prepared by adding an appropriate amount of Macrogol 4000 30 g and Macrogol 400 to 0.3 g of a heparinoid, 0.5 g of tocopherol acetate, 0.2 g of allantin and 1.0 g of diphenhydramine.
3. 3. Preparation of gel preparation A gel preparation was prepared by adding 40 g of ethanol, 0.5 g of hypromellose, 0.5 g of hydroxyethyl cellulose, and an appropriate amount of purified water to 0.3 g of a heparinoid, 0.5 g of tocopherol acetate, 0.2 g of allantin and 1.0 g of diphenhydramine.
The same effect as that shown in the cream was observed for each of the above compositions.
As described above, according to the present embodiment, it has been possible to provide an external preparation for skin capable of radically treating a dry skin disease accompanied by itching by suppressing itching and restoring the skin tissue to a normal state.

Claims (1)

(A) and heparinoid, (B) includes a tocopherol acetate, and (C) allantoin, and (D) diphenhydramine, and (E) stearyl alcohol, and (F) white Waseri emissions, (G) chlorhexidine hydrochloride, Topical skin preparations that are creams free of benzalkonium chloride, benzethonium chloride, depotassium chloride, biosols and phenolic fungicides , panthenol and squalane.